Analysis of mobility level of COVID-19 patients undergoing mechanical ventilation support: A single center, retrospective cohort study

Background Severe coronavirus disease 2019 (COVID-19) patients frequently require mechanical ventilation (MV) and undergo prolonged periods of bed rest with restriction of activities during the intensive care unit (ICU) stay. Our aim was to address the degree of mobilization in critically ill patients with COVID-19 undergoing to MV support. Methods Retrospective single-center cohort study. We analyzed patients’ mobility level, through the Perme ICU Mobility Score (Perme Score) of COVID-19 patients admitted to the ICU. The Perme Mobility Index (PMI) was calculated [PMI = ΔPerme Score (ICU discharge–ICU admission)/ICU length of stay], and patients were categorized as “improved” (PMI > 0) or “not improved” (PMI ≤ 0). Comparisons were performed with stratification according to the use of MV support. Results From February 2020, to February 2021, 1,297 patients with COVID-19 were admitted to the ICU and assessed for eligibility. Out of those, 949 patients were included in the study [524 (55.2%) were classified as “improved” and 425 (44.8%) as “not improved”], and 396 (41.7%) received MV during ICU stay. The overall rate of patients out of bed and able to walk ≥ 30 meters at ICU discharge were, respectively, 526 (63.3%) and 170 (20.5%). After adjusting for confounders, independent predictors of improvement of mobility level were frailty (OR: 0.52; 95% CI: 0.29–0.94; p = 0.03); SAPS III Score (OR: 0.75; 95% CI: 0.57–0.99; p = 0.04); SOFA Score (OR: 0.58; 95% CI: 0.43–0.78; p < 0.001); use of MV after the first hour of ICU admission (OR: 0.41; 95% CI: 0.17–0.99; p = 0.04); tracheostomy (OR: 0.54; 95% CI: 0.30–0.95; p = 0.03); use of extracorporeal membrane oxygenation (OR: 0.21; 95% CI: 0.05–0.8; p = 0.03); neuromuscular blockade (OR: 0.53; 95% CI: 0.3–0.95; p = 0.03); a higher Perme Score at admission (OR: 0.35; 95% CI: 0.28–0.43; p < 0.001); palliative care (OR: 0.05; 95% CI: 0.01–0.16; p < 0.001); and a longer ICU stay (OR: 0.79; 95% CI: 0.61–0.97; p = 0.04) were associated with a lower chance of mobility improvement, while non-invasive ventilation within the first hour of ICU admission and after the first hour of ICU admission (OR: 2.45; 95% CI: 1.59–3.81; p < 0.001) and (OR: 2.25; 95% CI: 1.56–3.26; p < 0.001), respectively; and vasopressor use (OR: 2.39; 95% CI: 1.07–5.5; p = 0.03) were associated with a higher chance of mobility improvement. Conclusion The use of MV reduced mobility status in less than half of critically ill COVID-19 patients.


MAJOR COMMENT Introduction
The whole introduction is well-written and easy to follow. I recommend adding some studies that reported the poor outcomes of low mobility level or late mobilization in a hospital to emphasize the importance of conducting the current study. The authors agree with the suggestion to add some studies in order to report mobility level, physical and clinical outcomes after episode of critical illness. We included three studies into "introduction" section, as follows: "The consequences are frequently observed among ICU survivors, with impairment physical and psychological recovery [Boelens et al. (2022)]. Early mobilization and rehabilitation have been shown to be effective in enhancing the recovery of critically ill patients, but more large-scale, multicenter randomized controlled trials are required to further confirm these findings [Monsees et al. (2022)]. Although the present available evidence of early rehabilitation still remains inconsistent; on the overall evidence rehabilitation interventions should not be delayed [Wang et al. (2020)]." Methods 1. Based on the title, I assume that this study only included patients with "severe" COVID-19. How did you determine the severity? Please define it in the inclusion criteria.
After read your comment, the authors considered the topic of "inclusion criteria" inconsistent. We would like to clarify that not only "severe" cases of COVID-19 were included in the present study. We included all patients with COVID-19 diagnosis (e.g., mild, moderate, and severe) cases that required ICU admission.
We decided to provide additional information about the inclusion criteria adopted, as follows: "We considered all ICU admissions of COVID-19 diagnosis (e.g., mild, moderate, and severe) during the study period eligible for inclusion. The following inclusion criteria were used: 1) age ≥ 18 years; and 2) confirmed diagnosis of COVID-19 by reverse transcription-polymerase chain reaction (RT-PCR) for SARS-CoV-2 [20]. We excluded patients with missing core data, defined as the use of MV during ICU stay and report of mobility status at ICU admission and/or discharge". We hope this modification meets your suggestion for further clarification regarding the inclusion criteria adopted, improving readers understand.

Please describe the general physiotherapy program.
The general physiotherapy program at Hospital Israelita Albert Einstein, consists in five levels of activity therapy. The advance through levels 1 through 5, is based on patients' ability to execute tasks gradually complex, followed by increase of muscle strength and less dependence to execute the proposed activities and exercises. There is a gradual progression on patients' physical function status, as briefly presented below: • Level "1", is considered when patients were unconscious and restrict to bed. Only passive range of motion therapy, stretching, and positioning is administered to all upper and lower extremity joints. The use of equipment such as neuromuscular electrical stimulation (NMES), and passive mode of cycle ergometer can be used as part of physiotherapy interventions. • Level "2", is considered when patients are able to sit at side of bed. They progress to active-assistive and active range of motion exercise as they are alert and able to advance their participation during physiotherapy interventions.
• Level "3", patients are able to stand and, in some cases, transfer to edge of bed. As patients progressed, the activities will be more complex, increasingly focused on functional activities, requiring more attention, coordination, and performance. • Level "4", will be considered for those patients who are able to execute pre-gait activities (e.g., forward and lateral weight shifting, marching in place) and ambulation initiate for short distances. They gradually require less assistance to ambulate for greater distances. • Level "5", patients are ambulating without any assistance or use of gait devices. The focus at this stage is prepare the patient to be discharged home, educating them how to maintain the functional independence, and activities of daily living.

I was wondering what the Minimal clinically important difference (MCID) of Perme Score or Perme Mobility Index (PMI) is. Was there any previous study considering "PMI>0" as improvement in mobility?
Thanks for your comment. This single-center study conducted with ICU patients, determined the value of 1.36 points of the Perme Score, to be able to detect changes on patients' mobility status. This value can be considered questionable, due to the narrow value presented, once the Perme Score total points range from "0" up to "32" points. However, to our knowledge, this is the only available publication establishing the MCID for the Perme Score.
Additionally This new concept of the "Perme Mobility Index (PMI)" established values of "PMI>0" as improvement in mobility status, once it is calculated, as presented below: "[PMI = ΔPerme Score (ICU discharge -ICU admission)/ICU length of stay]". Based on the PMI, patients can be divided into two groups: "Improved mobility status" (PMI > 0) and "Not improved mobility status" (PMI ≤ 0). Thus, the "positive" values (e.g., PMI > 0) must be interpreted with Perme Score at ICU discharge greater than the Perme Score at ICU admission. The "negative" values (e.g., PMI ≤ 0) must be interpreted with Perme Score at ICU discharge lower than the Perme Score at ICU admission.
4. The sample size was quite large. Why did the authors still decide to report the median and interquartile range rather than the mean and standard deviation?
We appreciate the reviewer's comment. Indeed, the sample size of the present study can be considered "quite large" (n = 949). The results are reported as median and interquartile range, because according to our statistical analysis, the normality was assessed by the Kolmogorov-Smirnov test. We included this information for readers better understanding, as follows: "Continuous variables are presented as median and interquartile range (IQR), and categorical variables as absolute and relative frequencies. Normality was assessed by the Kolmogorov-Smirnov test."